This proposal seeks to correlate biochemistry with altered motor function, using functional biochemical indices such transmitter turnover and metabolite concentrations in addition to steady-state concentrations of transmitter with both turning behavior and spontaneous motor activity. During the first years of this project, we unexpectedly found that unilateral lesions of 5-HT pathways led to a turning syndrome typical of dopaminergic hyperfunction, associated with clearly increased dopamine synthesis on the side of the lesion. This turning differs from that described by Ungerstedt because apomorphine and amphetamine cause turning in the same direction, unlike the situation found after lesions of the DA pathways. Even more unexpected was the fact that these rats invariably recover in a few weeks and that chemical recovery correlates nicely with motor function. We are now attempting to develop a multi-dimensional analysis of the effects of selective brain lesions and the basis for recovery, when it occurs. Our focus continues to be on the so-called extrapyramidal motor system and our work will be relevant to human diseases characterized by chorea, dystonia, and involuntary movements. Since the anatomy of the forebrain monoamine systems and their origins remains incompletely known, we can not understand our results without undertaking morphological studies. For example, both the median raphe nucleus (MRN) and the larger dorsal raphe nucleus (DRN) send known inputs to the nigrostriatal system at one or another level, yet only MRN lesions produce turning and increased responsiveness to amphetamine. We have strong indications that cellular basis for recovery differs depending upon whether the initial lesions was made in a cell body region or a terminal field. We wish to develop a detailed anatomical picture of what happens with both kinds of lesions. We also want to study the effects of tryptophan treatment and tryptophan deficient diets upon these rats: will tryptophan loading enhance recovery? Can deficiency of this precursor restore the lesion in a recovered animal?